Pmg. Neuro-Psychopharmocol. 8 Biol. Psychiot. 1986, Vol. 10, pp. 599-610 0278-5846/86 $0.00 + .50 Printed in Great Britain. 1986 Pergamon Journals Ltd. PHARMACOLOGIC MODELLING OF ALZHEIMER’S DISEASE TREY SUNDERLAND, PIERRE N. TARIOT, HERBERT WEINGARTNER, DENNIS L. MURPHY, PAUL A. NEWHOUSE. EDWARD A. MUELLER and ROBERT M. COHEN Laboratory of Clinical Science, National Institute of Mental Health Bethesda, Maryland, U.S.A. (Final form, February, 1986) Contents 1. 2. 2.1. 2.2. 2.3. 3. 3.1. 3.2. 3.2.1. 3.2.2. 3.2.3. 3.3. 4. Abstract Introduction Chnlinergic Factors in Der-entia of the Alzheiner Type Non-Cholinergic Drugs and Memory Cholinergic Drugs and Human Memory Cholinergic Drugs in Animal Models Anticholinergic Modelling of Dementia Pharmacology of Scopolamine Scopolamine Testing in Elderly Controls Subjects Methods Results Cognitive Sensitivity of Elderly: Comparison to Alzheimer's Uisease Conclusions Acknowledgements References 599 600 600 600 601 603 603 604 605 605 605 605 605 606 606 607 Abstract Sunderland, Trey, Pierre N. Tariot, Herbert Weingartner, Dennis L. Murphy, Paul A. Newhouse, Edward A. Mueller and Robert M. Cohen: Pharmacologic modelling of Alzheimer's disease. Prog. Neuro-Psychopharmacol. and Biol. Psychiat. 1986, lo (3-5): 599-610. 1. 2. 3. 4. Evidence pointing to the central role nf the cholinergic system in nornal human memory function and disorders such as Alzheiner's disease has grown tremendously in recent years. Anticholinergic and non-cholinergic agents have heen found to create transient mpmnry impairments in young adults which mimic the changes asnciated with normal aging or amnesia. The rationale for using scopnlanine, a centrally active antichnlinergic agent, as a pharmacologic probe of memory function is reviewed using data from studies in animals and hunans. The cognitive functioning of nnrnal elderly controls given scopolamine is compared to the baseline functioning of patients with Alzheimer's disease, followed by a discussion of the use of scopolamine as a modelling agent for dementia. Keywords: anticholinergic, cognitive sensitivity, dementia of the Alzheimer type, muscarinic antagonist, scopolamine, Abbreviations: dementia of the Alzheimr type (DAT), Short Portable Mental Status Questionaire (SPMSQ), Wechsler Adult Intelligence Scale (CIAIS). 599